8 results on '"Jørgensen, Steffen"'
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2. Pharmacogenetic testing of CYP2D6, CYP2C19 and CYP2C9 in Denmark:Agreement between publicly funded genotyping tests and the subsequent phenotype classification
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Baltzer Houlind, Morten, Hansen, Luise, Iversen, Esben, Rasmussen, Henrik Berg, Larsen, Jens Borggaard, Jørgensen, Steffen, Dalhoff, Kim, Damkier, Per, Walls, Anne B., Vermehren, Charlotte, Andersen, Trine Rune Høgh, Kallemose, Thomas, Christrup, Lona, Westergaard, Niels, Baltzer Houlind, Morten, Hansen, Luise, Iversen, Esben, Rasmussen, Henrik Berg, Larsen, Jens Borggaard, Jørgensen, Steffen, Dalhoff, Kim, Damkier, Per, Walls, Anne B., Vermehren, Charlotte, Andersen, Trine Rune Høgh, Kallemose, Thomas, Christrup, Lona, and Westergaard, Niels
- Abstract
The cytochrome P450 (CYP) enzyme family catalyses the metabolism of approximately 80% of all medications.1, 2 Many genes encoding the CYP enzymes exhibit high levels of polymorphism that affect their expression and activity. The most frequent and clinically important variations exist within the genes CYP2D6, CYP2C19 and CYP2C9.1 CYP2D6, the most extensively studied drug-metabolizing enzyme, has over 100 allelic variants and is responsible for metabolizing about 25% of all marketed medications.1, 3 CYP2C19 and CYP2C9 are collectively responsible for metabolizing about 20% of medications. It is estimated that 74%–97% of Caucasian individuals possess at least one genetic variation in the CYP gene, potentially affecting metabolism for about one quarter of all prescribed medications.4 Testing for this genetic variation can help identify individuals for whom medication safety and efficacy can be improved through dose adjustment.1 Pharmacogenetic (PGx) testing assesses genetic variation by identifying a patient's genotype and assigning a predicted phenotype. The predicted phenotype of an inherited allele can be classified as loss of function, decreased function, normal function or increased function.3 Numerous PGx tests have been developed for both public and private use. The evidence for whether these tests actually improve treatment outcomes is controversial, but a large implementation study recently showed that pre-emptive PGx testing may reduce the incidence of adverse reactions.5 PGx tests are normally based on genotyping panels with predefined alleles, but variations in these panels between PGx providers and in the approach for genotype-to-phenotype translation can result in conflicting recommendations.6, 7 Current guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend classifying phenotypes into four, five and three categories for CYP2D6, CYP2C19 and CYP2C9, respectively.8 Despite these recommendations, a recent st
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- 2024
3. Nitrite accumulation and anammox bacterial niche partitioning in Arctic Mid-Ocean Ridge sediments
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Zhao, Rui, Babbin, Andrew R, Roerdink, Desiree L, Thorseth, Ingunn H, Jørgensen, Steffen L, Zhao, Rui, Babbin, Andrew R, Roerdink, Desiree L, Thorseth, Ingunn H, and Jørgensen, Steffen L
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By consuming ammonium and nitrite, anammox bacteria form an important functional guild in nitrogen cycling in many environments, including marine sediments. However, their distribution and impact on the important substrate nitrite has not been well characterized. Here we combined biogeochemical, microbiological, and genomic approaches to study anammox bacteria and other nitrogen cycling groups in two sediment cores retrieved from the Arctic Mid-Ocean Ridge (AMOR). We observed nitrite accumulation in these cores, a phenomenon also recorded at 28 other marine sediment sites and in analogous aquatic environments. The nitrite maximum coincides with reduced abundance of anammox bacteria. Anammox bacterial abundances were at least one order of magnitude higher than those of nitrite reducers and the anammox abundance maxima were detected in the layers above and below the nitrite maximum. Nitrite accumulation in the two AMOR cores co-occurs with a niche partitioning between two anammox bacterial families (Candidatus Bathyanammoxibiaceae and Candidatus Scalinduaceae), likely dependent on ammonium availability. Through reconstructing and comparing the dominant anammox genomes (Ca. Bathyanammoxibius amoris and Ca. Scalindua sediminis), we revealed that Ca. B. amoris has fewer high-affinity ammonium transporters than Ca. S. sediminis and lacks the capacity to access alternative substrates and/or energy sources such as urea and cyanate. These features may restrict Ca. Bathyanammoxibiaceae to conditions of higher ammonium concentrations. These findings improve our understanding about nitrogen cycling in marine sediments by revealing coincident nitrite accumulation and niche partitioning of anammox bacteria.
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- 2024
4. Distribution of the cytochrome P450 *alleles for CYP2C9 and CYP2C19 in a cohort of the Danish Blood Donor Study determined by using the Illumina Infinium Global Screening Array.
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Jørgensen, Steffen, Brodersen, Thorsten, Vesterager Pedersen, Ole Birger, and Westergaard, Niels
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CYTOCHROME P-450 , *CYTOCHROME P-450 CYP2C19 , *BLOOD donors , *GENETIC regulation , *GENETIC variation , *CYTOCHROME c - Abstract
This article presents a study on the distribution of cytochrome P450 (CYP450) alleles in the Danish population. CYP450 enzymes are important for drug metabolism, and genetic variations in the genes encoding these enzymes can impact drug response. The study compared genotype data from different genotyping platforms and found that the CYP2C19*17 and CYP2C9*2 alleles were more common than the CYP2C19*2 and CYP2C9*3 alleles. The results provide valuable insights into the genetic variability of these enzymes in the Danish population and suggest that the Illumina GSA platform could be useful for identifying drug-gene interactions. [Extracted from the article]
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- 2024
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5. Iron Oxyhydroxide‐Rich Hydrothermal Deposits at the High‐Temperature Fåvne Vent Field, Mohns Ridge.
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Gini, Caroline, Jamieson, John W., Reeves, Eoghan P., Gartman, Amy, Barreyre, Thibaut, Babechuk, Michael G., Jørgensen, Steffen L., and Robert, Katleen
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HYDROTHERMAL deposits ,MID-ocean ridges ,SUBMARINE volcanoes ,OXIDE minerals ,ORE deposits ,SULFIDE minerals ,DEEP-sea exploration - Abstract
The recently discovered Fåvne vent field, located at 3,040 m depth on the slow‐spreading Mohns mid‐ocean ridge between Greenland and Norway, is a high‐temperature (≥250°C) vent field that is characterized by Fe oxyhydroxide‐rich and S‐poor chimneys and mounds. The vent field is located on both the hanging wall and footwall of a normal fault with a ∼1.5 km throw that forms the western edge of the ∼20 km wide ridge axial valley. Data collected during exploration of the site using a remotely operated vehicle as well as mineralogical and geochemical analyses of rock samples and sediments are used to characterize the geological setting of the vent field and composition of the hydrothermal deposits. The chimney walls are highly porous and lack defined chalcopyrite lined conduits, typical of high‐temperature chimneys. Overall, abundant Fe oxyhydroxide precipitation at high‐temperature vents at Fåvne reflects an excess of Fe over reduced S in the fluid, leading to precipitation of Fe oxide and oxyhydroxide minerals at high to moderate temperature vents (>100°C), and as microbially mediated and abiotic precipitation of Fe oxyhydroxide minerals at low‐temperature diffuse vents (<100°C). The mounds and chimneys exhibit low base metal and reduced S concentrations relative to globally averaged seafloor deposits and suggest subseafloor mixing of hydrothermal fluid with seawater, causing metal sulfide precipitation. Cobalt enrichment at Fåvne may reflect a subsurface influence of an ultramafic substrate on circulating fluids, although ultramafic rocks are absent on the seafloor and no other elements typical of ultramafic deposits are present. Plain Language Summary: Seafloor hydrothermal deposits are mineral deposits formed from seawater penetrating the oceanic crust and becoming enriched in metals by leaching the surrounding rocks as the temperature rises close to a heat source. Once heated, the fluid rises back to the seafloor where it comes into contact with cold seawater and the metals precipitate, forming chimneys and mounds. The minerals and metal concentrations record temperatures of formation and environments, and can help us understand the processes associated with plate tectonics and the formation of ore deposits. Using underwater vehicles, we collected rocks and sediments from the Fåvne vent field and measured the temperature of the chimneys, mounds, and surrounding seafloor to understand how these deposits form on the seafloor. The Fåvne vent field differs from other vent fields because it is enriched in iron‐rich‐minerals and depleted in sulfur‐rich‐minerals. The dominance of iron‐rich minerals and the abundance of fractures in the seafloor at the vent field suggest that the hydrothermal fluid is cooled by seawater percolating along the fractures, accumulating these metals in the subsurface instead of at the seafloor. This process is important for understanding the current land‐based mineral deposits being mined today and for the exploration of seafloor mineral deposits. Key Points: The Fåvne vent field consists of chimneys and mounds composed of Fe oxyhydroxide minerals with minor sulfide mineralsVenting of hot fluids with temperatures up to 267°C is dominantly diffuse, sustaining significant microbial communitiesLow base metal concentrations of the Fåvne deposits suggest subsurface seawater mixing and mineral precipitation [ABSTRACT FROM AUTHOR]
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- 2024
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6. Pharmacogenetic testing of CYP2D6, CYP2C19 and CYP2C9 in Denmark: Agreement between publicly funded genotyping tests and the subsequent phenotype classification.
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Houlind, Morten Baltzer, Hansen, Luise, Iversen, Esben, Rasmussen, Henrik Berg, Larsen, Jens Borggaard, Jørgensen, Steffen, Dalhoff, Kim, Damkier, Per, Walls, Anne B., Vermehren, Charlotte, Andersen, Trine Rune Høgh, Kallemose, Thomas, Christrup, Lona, and Westergaard, Niels
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CYTOCHROME P-450 CYP2C19 ,PHENOTYPES ,CYTOCHROME P-450 CYP2D6 ,PHARMACOGENOMICS ,CLINICAL decision support systems ,CLASSIFICATION - Abstract
This document summarizes a pilot study conducted in Denmark to assess the agreement between publicly funded genotyping tests and phenotype classification for certain genes. The study found inconsistencies in genotype and phenotype agreement between three laboratories, highlighting the need for standardization in pharmacogenetic testing. The document also discusses the lack of national alignment between laboratories in Denmark, which poses challenges in the use and implementation of pharmacogenetic testing. The study recommends continuous updating of the phenotype approach and alignment of genotyping and phenotyping classifications to ensure consistent implementation of pharmacogenetic testing in Denmark. The document also references various guidelines and studies related to pharmacogenetic testing in mental health care settings. [Extracted from the article]
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- 2024
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7. Hydrothermal activity fuels microbial sulfate reduction in deep and distal marine settings along the Arctic Mid Ocean Ridges.
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Roerdink, Desiree L., Vulcano, Francesca, Landro, Jan-Kristoffer, Moltubakk, Karen E., Babel, Hannah R., Jørgensen, Steffen Leth, Baumberger, Tamara, Økland, Ingeborg E., Reeves, Eoghan P., Thorseth, Ingunn H., Reigstad, Laila J., Strauss, Harald, and Steen, Ida H.
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COLD seeps ,MARINE sediments ,SULFATES ,SULFUR isotopes ,PORE fluids ,SULFUR cycle ,MID-ocean ridges - Abstract
Microbial sulfate reduction is generally limited in the deep sea compared to shallower marine environments, but cold seeps and hydrothermal systems are considered an exception. Here, we report sulfate reduction rates and geochemical data from marine sediments and hydrothermal vent fields along the Arctic Mid Ocean Ridges (AMOR), to assess the significance of basalt-hosted hydrothermal activity on sulfate reduction in a distal deep marine setting. We find that cored marine sediments do not display evidence for sulfate reduction, apart from low rates in sediments from the Knipovich Ridge. This likely reflects the overall limited availability of reactive organic matter and low sedimentation rates along the AMOR, except for areas in the vicinity of Svalbard and Bear Island. In contrast, hydrothermal samples from the Seven Sisters, Jan Mayen and Loki's Castle vent fields all demonstrate active microbial sulfate reduction. Rates increase from a few 10s to 100s of pmol SO
4 2- cm-3 d-1 in active hightemperature hydrothermal chimneys, to 10s of nmol SO4 2- cm-3 d-1 in lowtemperature barite chimneys and up to 110 nmol cm-3 d-1 in diffuse venting hydrothermal sediments in the Barite field at Loki's Castle. Pore fluid and sediment geochemical data suggest that these high rates are sustained by organic compounds from microbial mats and vent fauna as well as methane supplied by high-temperature hydrothermal fluids. However, significant variation was observed between replicate hydrothermal samples and observation of high rates in seemingly inactive barite chimneys suggests that other electron donors may be important as well. Sediment sulfur isotope signatures concur with measured rates in the Barite field and indicate that microbial sulfate reduction has occurred in the hydrothermal sediments since the recent geological past Our findings indicate that basalt-hosted vent fields provide sufficient electron donors to support microbial sulfate reduction in high- and low-temperature hydrothermal areas in settings that otherwise show very low sulfate reduction rates. [ABSTRACT FROM AUTHOR]- Published
- 2024
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8. Pharmacogenetic testing of CYP2D6, CYP2C19 and CYP2C9 in Denmark: Agreement between publicly funded genotyping tests and the subsequent phenotype classification.
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Baltzer Houlind M, Hansen L, Iversen E, Rasmussen HB, Larsen JB, Jørgensen S, Dalhoff K, Damkier P, Walls AB, Vermehren C, Andersen TRH, Kallemose T, Christrup L, and Westergaard N
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- Cytochrome P-450 CYP2C9 genetics, Genotype, Cytochrome P-450 CYP2C19 genetics, Phenotype, Denmark, Cytochrome P-450 CYP2D6 genetics, Pharmacogenomic Testing
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- 2024
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- View/download PDF
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